Objective: Establishing a long-term neurotoxic model to explore the mechanism of neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) and the putative protection conferred by Vit C against oxidative stress harm.
Methods: Male Wistar rats were randomly assigned to control group (A) and MDMA treatment groups(B, C, D, E). Rats of group B were given MDMA 20 mg/kg; groups C, D, E were given Vit C 250 mg/kg 30 min before administration of MDMA (Vit C 30 min group) and 3 h (Vit C 3 h group) and 5 h (VitC 5 h group) after administration of MDMA, respectively. Rats of control group were treated with the same volume of saline. Concentrations of ATP and ADP in brain cortex and 5-HT in hippocampus and occipital cortex were measured by high perfor-mance liquid chromatography; the expression of SERT mRNA was detected by in situ hybridization; and the expression of protein GFAP was detected by immunohisto-chemistry.
Results: hours after MDMA treatment, the concentration of ATP in brain cortex was lessened, compared with control (P <0.05). On the 7th day after MDMA treatment, the concentration of 5-HT in rat hippocampus and occipital cortex was decreased, compared with control (P<0.05). The expression of SERT mRNA in hippocampus was decreased, whereas the expression of GFAP in brain tissue was increased (P<0.05). The adminstration of Vit C 30 min before MDMA treatment and 3 h after MDMA treatment did not curb the decrease of ATP, 5-HT and the expression of SERT mRNA, but Vit C administrated 5 h after MDMA treatment could curb the decrease of ATP and the functional markers of 5-HT. And Vit C given at three time points did downregulate the GFAP expression.
Conclusion: MDMA could deplete the direct energetic substance ATP. MDMA could exert neurotoxic effect on 5-HT system. Vit C given 5 h after MDMA administration could provide neuroprotection for ATP and 5-HT system.